In the last decade, combined ultrasound and photoacoustic (USPA) imaging - a synergistic and complementary combination of two ultrasound-based techniques, has been introduced and is now gaining wide acceptance in both pre-clinical and clinical arenas. USPA is capable of simultaneous visualization of anatomical/morphological structures and functional information about the tissue. Furthermore, either ultrasound or photoacoustic targeted contrast agents have been used to enable cellular and molecular sensitivity of USPA imaging. However, to utilize the entire spectrum of benefits offered by multi-modal USPA imaging, dual-contrast agents are required. Overall, there is a need for molecularly targeted nanoscaled agent capable of extracellular and intracellular delivery, and, more importantly, a contrast enhancement for both ultrasound and photoacoustic imaging. The overall theme of our project is to develop and commercialize a highly-sensitive, molecularly-specific nanoscaled imaging contrast agent for USPA imaging. The proposed contrast agent consists of gold nanoparticles in liquid perfluorocarbon (PFC) core encapsulated within a lipid layer. The contrast agent will be targeted to a particular receptor of interest (e.g, human epidermal growth factor receptor (EGFR) for breast and many other cancers) resulting in molecular sensitivity of the proposed contrast agent. The main advantage of PAnDs is their unique and inherent multi-modal nature leading to an increase in the signal-to-noise ratio, thus enhancing the resolution and molecular sensitivity of USPA imaging. The goal of our current phase I SBIR project is focused on the development and initial optimization of stable, dual-contrast USPA agents with properties needed to enable in-vivo molecular USPA imaging. The end goal of our overall (phase I and phase II) SBIR project is to produce ready-to-commercialize dual-contrast agents optimized for molecular imaging, long shelf-life, and overall stability. Our particles would be the first commercial agents designed and developed specifically to support molecular, dual-contrast USPA imaging. Proprietary and Confidential Property of NanoHybrids LLC PUBLIC HEALTH RELEVANCE: The overall goal of our application is to develop and test a ready-to-commercialize dual-contrast agent suitable for molecular specific ultrasound and photoacoustic (USPA) imaging. In molecular USPA imaging, targeted nano-sized contrast agents are injected intravenously, and gray-scale ultrasound and photoacoustic imaging are used to simultaneously assess morphological, functional and molecular properties of tissue. Proprietary and Confidential Property of NanoHybrids LLC